Study of Denosumab vs. Zoledronic Acid to Treat Bone Metastases in Men With Hormone-refractory Prostate Cancer - Full Text View

Purpose

The purpose of this study is to determine if denosumab is non-inferior to zoledronic acid (Zometa®) in the treatment of bone metastases in men with hormone-refractory prostate cancer

Condition	Intervention	Phase
Bone Metastases	Drug: zoledronic acid Biological: denosumab	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Supportive Care
Official Title:	A Randomized, Double-Blind, Multicenter Study of Denosumab Compared With Zoledronic Acid (Zometa®) in the Treatment of Bone Metastases in Men With Hormone-Refractory Prostate Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Hormones Prostate Cancer

Drug Information available for: Zoledronic acid Denosumab

Genetic and Rare Diseases Information Center resources: Bone Cancer

U.S. FDA Resources

Further study details as provided by Amgen:

Primary Outcome Measures:

Time to the First On-Study SRE (Non-inferiority) [ Time Frame: Up to 40.5 months ] [ Designated as safety issue: No ]
Time to the first on-study skeletal-related event (SRE) analyzed for non-inferiority. Kaplan-Meier estimates of the median and its dispersion are reported.

Secondary Outcome Measures:

Time to the First On-Study SRE (Superiority) [ Time Frame: Up to 40.5 months ] [ Designated as safety issue: No ]
Time to the first on-study skeletal-related event (SRE), analyzed for superiority of denosumab. Kaplan-Meier estimates of the median and its dispersion are reported.
Time to the First-And-Subsequent On-Study SRE [ Time Frame: Up to 40.5 months ] [ Designated as safety issue: No ]
Time to the first-and-subsequent on-study skeletal-related event (SRE), analyzed for superiority of denosumab using multiple event analysis, the event must occur at least 21 days after the previous SRE.

This outcome measure utilizes multiple event times, was analyzed based on a proportional mean model, and is therefore more appropriately summarized by the cumulative mean number of events.


Enrollment:	1904
Study Start Date:	April 2006
Study Completion Date:	February 2012
Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: zoledronic acid	Drug: zoledronic acid Q4W 4 mg zoledronic acid IV over minimum 15 minutes and 120 mg denosumab placebo SC Other Name: Zometa
Experimental: denosumab	Biological: denosumab Q4W 120 mg denosumab SC and 4 mg zoledronic acid placebo IV over a minimum of 15 minutes

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Men >/= 18 years of age with histologically confirmed prostate cancer
Radiographic evidence of at least one bone metastasis
Failure of at least one hormonal therapy as evidenced by a rising PSA
Serum testosterone level of <50 ng/dL
ECOG PS 0, 1, or 2
Adequate organ function

Exclusion Criteria:

Current or prior IV bisphosphonate administration
Current or prior oral bisphosphonates for bone mets
Life expectancy of less than 6 months

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00321620

Sponsors and Collaborators

Amgen

Investigators


Study Director:	MD	Amgen

More Information

Additional Information:

Notice regarding posted summaries of trial results This link exits the ClinicalTrials.gov site

AmgenTrials clinical trials website This link exits the ClinicalTrials.gov site

No publications provided by Amgen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

de Liaño AG, Reig O, Mellado B, Martin C, Rull EU, Maroto JP. Prognostic and predictive value of plasma testosterone levels in patients receiving first-line chemotherapy for metastatic castrate-resistant prostate cancer. Br J Cancer. 2014 Apr 29;110(9):2201-8. doi: 10.1038/bjc.2014.189. Epub 2014 Apr 10.

von Moos R, Body JJ, Egerdie B, Stopeck A, Brown JE, Damyanov D, Fallowfield LJ, Marx G, Cleeland CS, Patrick DL, Palazzo FG, Qian Y, Braun A, Chung K. Pain and health-related quality of life in patients with advanced solid tumours and bone metastases: integrated results from three randomized, double-blind studies of denosumab and zoledronic acid. Support Care Cancer. 2013 Dec;21(12):3497-507. doi: 10.1007/s00520-013-1932-2. Epub 2013 Aug 22.

Lipton A, Fizazi K, Stopeck AT, Henry DH, Brown JE, Yardley DA, Richardson GE, Siena S, Maroto P, Clemens M, Bilynskyy B, Charu V, Beuzeboc P, Rader M, Viniegra M, Saad F, Ke C, Braun A, Jun S. Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer. 2012 Nov;48(16):3082-92. doi: 10.1016/j.ejca.2012.08.002. Epub 2012 Sep 10.

Fizazi K, Carducci M, Smith M, Damião R, Brown J, Karsh L, Milecki P, Shore N, Rader M, Wang H, Jiang Q, Tadros S, Dansey R, Goessl C. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet. 2011 Mar 5;377(9768):813-22. doi: 10.1016/S0140-6736(10)62344-6. Epub 2011 Feb 25.


Responsible Party:	Amgen
ClinicalTrials.gov Identifier:	NCT00321620 History of Changes
Other Study ID Numbers:	20050103
Study First Received:	May 2, 2006
Results First Received:	December 10, 2010
Last Updated:	February 4, 2014
Health Authority:	Argentina: Ministry of Health Australia: Therapeutic Goods Administration Austria: Secretariat of Health Belgium: Pharmaceutical Inspectorate Brazil: Ministry of Health Bulgaria: Ministry of Health Canada: Health Products and Food Branch Chile: Health Ministry Czech Republic: State Institute for Drug Control Denmark: Ministry of Health Estonia: State Agency of Medicines France: Ministry of Health Germancy: Federal Institute for Drugs and Medical Devices Greece: National Organization for Medicines Guatemala: Ministry of Health Hungary: Ministry of Health, Social and Family Affairs Israel: Ministry of Health Italy: Ministry of Health Latvia: State Agency of Medicines Lithuania: Ministry of Health Mexico: Ministry of Health Netherlands: Medicines Evaluation Board Norway: Norwegian Medicines Agency Panama: Ministry of Health, Peru: Ministry of Health Poland: Drug Institut Portugal: National Institute of Pharmacy and Medicines Russia: Ministry of Health Slovakia: Ministry of Health South Africa: Department of Health Spain: Spanish Drug Agency Sweden: Medical Products Agency Switzerland: Agency for Therapeutic Products Turkey: Ministry of Health Ukraine: Ministry of Health United Kingdom: Medicines and Healthcare Products Regulatory Agency United States: Food and Drug Administration Romania: Ministry of Health and the Family

Keywords provided by Amgen:


Bone metastases Hormone-refractory prostate cancer Skeletal	Fractures Compressions Bisphosphonates

Additional relevant MeSH terms:


Bone Marrow Diseases Bone Neoplasms Neoplasm Metastasis Prostatic Neoplasms Bone Diseases Genital Diseases, Male Genital Neoplasms, Male Hematologic Diseases Musculoskeletal Diseases Neoplasms	Neoplasms by Site Neoplastic Processes Pathologic Processes Prostatic Diseases Urogenital Neoplasms Diphosphonates Zoledronic acid Bone Density Conservation Agents Pharmacologic Actions Physiological Effects of Drugs

ClinicalTrials.gov processed this record on March 03, 2015